Drug development and CNS 1 Flashcards
What was found wrong with Elixir Sulphanilamide in 1937
Found to be contaminated by diethylene glycol, killing 107 people
What was found wrong with Sulfathiazole in 1941
Cross contamination with phenobarbital causing 300 deaths
What was the thalidomide controvsy in 1960
What was the thalidomide controversy in 1960
Was a sleeping tablet, caused 10,000-20,000 birth defects
What’s the first stage of a clinical trial
Basic research target selection and pre-clinical research
How long does the first stage of a clinical trial take
3- 6 years
What is the second stage of a clinical trial
Clinical research phase 1 (healthy individuals)
Clinical research phase (patients for the first time)
Phase 3
How long does the second stage take
6-7 years
What’s the last stage of a clinical trial and how long does it take
Regulatory review (0.5 - 2 years)
How long and how much money can you spend on a clinical trial
15 years and 1 billion
What are the lead findings in drug trials
Exploring toxicology, safety
How do you create a controlled environment in preclinical development
Providing a safety margin, defining the dose, defining a maximum dose, obtaining regulatory approval of clinical
What does LD50 mean and when was this carried out
Increase the dose until 50% died, in 1920
Now what rule is implemented
3R - reduce, refine, replace
What is the default non rodent
Beagle
What are the three dose groups
Low (no toxicity), intermediate, high
What are the general toxicology’s
Clinical pathology, haematology, kidney and liver function, coagulation
What are the goals for non-clinical safety evaluations
On/ off targets, reversibility, max nontoxic dose and min affective dose, identification of specific monitoring requirements
Examples of withdrawn drugs
Sibutramine (appetite suppressant)
Propoxyphene
Drotecogin
Rimonabant
Hydromorphone
Characteristics of a small molecule drug
Low molecular weight, chemically synthesised, well-defined structure
Characteristics of a biological molecule and monoclonal antibodies
High molecular weight, derived from living organisms, large and complex structure
How much have biologics accounted for in new medicine approvals
one third
Examples of vaccines
HPV, COVID-19
What are RNAi
interfering RNA molecules
What are cell based therapies
Taking a whole cell out of a patient, modify then grow. Then inject back into patient
Example for when cell based therapies are useful
Children with acute lymphoblastic leukemi
Example of when cell based therapies are useful
Children with acute lymphoblastic leukaemia
What is the phase 1 dose
Minimum anticipated biological effect
What is immunotherapy
A form of cancer treatment, uses immune system to attack cancer cells
What do checkpoint inhbitors do
Release natural brake on your immune system so that immune cells called t cells recognise and attack tumors